IGF1 drives Wnt-induced joint damage and is a potential therapeutic target for osteoarthritis.

Osteoarthritis is the most common joint disease and a global leading cause of pain and disability. Current treatment is limited to symptom relief, yet there is no disease-modifying therapy. Its multifactorial etiology includes excessive activation of Wnt signaling, but how Wnt causes joint destruction remains poorly understood.

Mechanical loading rescues mechanoresponsiveness in a human osteoarthritis explant model despite Wnt activation.

Objectives: Optimizing rehabilitation strategies for osteoarthritis necessitates a comprehensive understanding of chondrocytes' mechanoresponse in both health and disease, especially in the context of the interplay between loading and key pathways involved in osteoarthritis (OA) development, like canonical Wnt signaling. This study aims to elucidate the role of Wnt signaling in the mechanoresponsiveness of healthy and osteoarthritic human cartilage.

Methods: We used an ex-vivo model involving short-term physiological mechanical loading of human cartilage explants.

Fundamentals of osteoarthritis: Inflammatory mediators in osteoarthritis.

Objectives: As more has become known of the pathophysiology of osteoarthritis (OA), evidence that inflammation plays a critical role in its development and progression has accumulated. Here, we aim to review current knowledge of the complex inflammatory network in the OA joint.

Design: This narrative review is presented in three main sections: local inflammation, systemic inflammation, and therapeutic implications.

Innovation in Targeted Intra-articular Therapies for Osteoarthritis.

Osteoarthritis is the most common chronic joint disease characterized by progressive damage to the joints, leading to pain and loss of function. There is currently no cure or disease-modifying therapy for osteoarthritis. Hence, the increasing disease prevalence linked with ageing and obesity represents a substantial socio-economic burden.

Inhibition of KDM7A/B histone demethylases restores H3K79 methylation and protects against osteoarthritis.

Objectives: In osteoarthritis, methylation of lysine 79 on histone H3 (H3K79me), a protective epigenetic mechanism, is reduced. Histone methylation levels are dynamically regulated by histone methyltransferases and demethylases. Here, we aimed to identify which histone demethylases regulate H3K79me in cartilage and investigate whether their targeting protects against osteoarthritis.